We hypothesize that one or more susceptibility genes, other than APOE, increase the risk of Alzheimer's Disease (AD) among Caribbean Hispanics from the Dominican Republic. We propose to test this hypothesis by performing genetic linkage analysis in order to detect the chromosomal location of the susceptibility genes in Caribbean Hispanics. We intend to collect clinical information and obtain blood to establish cell lines on 80 to 90 affected Carribbean Hispanic sibpairs with AD each year for a total of 450 affected pairs (88 have been completed). We will also continue to search for families with multiple affected members. Within each sibship containing an affected AD sibpair, we shall also examine and obtain blood to establish cell lines from all living unaffected siblings. Cell lines will also be established from a representative sample of 200 individuals free of dementia evenly divided between Dominicans living in New York City and in the Dominican Republic. We propose to perform linkage analysis of AD using approximately 350 fluorescently labeled microsatellite markers, evenly spaced at an average of llcM across the human genome. We shall begin genotyping after the first 250 sibpairs are identified and will use the additional 200 sibpairs ascertained in this project to extend the genome search.